Genetic variation in the farnesoid X-receptor predicts Crohn's disease severity in female patients.

Scientific Reports
Aze WilsonRichard B Kim

Abstract

The farnesoid X receptor (FXR) is implicated in Crohn's disease (CD) pathogenesis. It is unclear how genetic variation in FXR impacts CD severity versus genetic variation in nuclear receptors such as pregnane X receptor (PXR) and the multi-drug resistance protein 1 (MDR1, ABCB1). To evaluate FXR-1G > T as a genomic biomarker of severity in CD and propose a plausible molecular mechanism. A retrospective study (n = 542) was conducted in a Canadian cohort of CD patients. Genotypic analysis (FXR-1G > T, MDR1 3435C > T and PXR -25385C > T) as well as determination of the FXR downstream product, fibroblast growth factor (FGF) 19 was performed. Primary outcomes included risk and time to first CD-related surgery. The effect of estrogen on wild type and variant FXR activity was assessed in HepG2 cells. The FXR-1GT genotype was associated with the risk of (odds ratio, OR = 3.34, 95% CI = 1.58-7.05, p = 0.002) and earlier progression to surgery (hazard ratio, HR = 3.00, 95% CI = 1.86-4.83, p < 0.0001) in CD. Female carriers of the FXR-1GT genotype had the greatest risk of surgery (OR = 14.87 95% CI = 4.22-52.38, p < 0.0001) and early progression to surgery (HR = 6.28, 95% CI = 3.62-10.90, p < 0.0001). Women carriers of FXR-1GT polymorphis...Continue Reading

References

Dec 24, 2005·Inflammatory Bowel Diseases·Elena UrcelayEmilio G de la Concha
Feb 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Takeshi InagakiSteven A Kliewer
May 5, 2006·Nature Reviews. Drug Discovery·Vera Regitz-Zagrosek
Jul 26, 2006·The American Journal of Gastroenterology·Charles N BernsteinJames F Blanchard
Oct 3, 2006·Inflammatory Bowel Diseases·Richard B GearryMurray L Barclay
Sep 11, 2007·Inflammatory Bowel Diseases·Alfonso MartínezElena Urcelay
Jun 13, 2008·Nature Protocols·Thomas D Schmittgen, Kenneth J Livak
Dec 17, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kwang-Hoon SongJohn Y L Chiang
Oct 30, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Piero VavassoriStefano Fiorucci
Nov 20, 2009·The New England Journal of Medicine·Clara Abraham, Judy H Cho
Sep 16, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alexandra MilonaCatherine Williamson
Mar 24, 2011·The American Journal of Gastroenterology·Henit Yanai, Stephen B Hanauer
Jun 3, 2011·World Journal of Pediatrics : WJP·Xiu-Qi ChenXiang Yun
Aug 11, 2011·Inflammatory Bowel Diseases·Jürgen GlasStephan Brand
Sep 3, 2011·PloS One·Rian M NijmeijerUNKNOWN Dutch Initiative on Crohn, Colitis (ICC)
Apr 12, 2013·Inflammatory Bowel Diseases·Junichi IwamotoYasushi Matsuzaki
Apr 1, 2014·Cell·Ronald M Evans, David J Mangelsdorf
Apr 15, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xiulong SongRuitang Deng
Jun 15, 2015·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Laurent Peyrin-BirouletBeth Rycroft
Feb 19, 2016·Nature Communications·Natalia Gomez-OspinaDavid D Moore
Jun 23, 2018·Cellular and Molecular Gastroenterology and Hepatology·Wendy A GoodmanTheresa T Pizarro

❮ Previous
Next ❯

Citations

Dec 9, 2020·Digestive Diseases and Sciences·Stefano FiorucciMichele Biagioli
Feb 11, 2021·International Journal of Molecular Sciences·Davide BanfiAndreina Baj

❮ Previous
Next ❯

Methods Mentioned

BETA
surgical resection
enzyme-linked immunosorbent assay
PCR
Assay
transfection
BSEP

Software Mentioned

SPSS
GraphPad Prism
R

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Trends in Pharmacological Sciences
Stefano FiorucciAngela Zampella
Histology and Histopathology
Ioannis KoutsounasS Theocharis
Histology and Histopathology
Yan-Dong WangWendong Huang
© 2021 Meta ULC. All rights reserved